Glutathione S-transferase gene T1 and ml polymorphism in type 2 diabetic patients with end-stage renal disease

ABSTRACT

Diabetes mellitus [DM] is associated with an increased production of reactive oxygen species [ROS] which may contribute to the development of diabetic nephropathy. Therefore, the levels of endogenous antioxidants may be one of determinants of the susceptibility to diabetic nephropathy. Glutathione S-transferases [GSTs] are enzymes involved in the metabolism of many disease-causing electrophilic substrates and protect the cells against oxidative stress. Genetic polymorphisms of the genes coding for enzymes result in different phenotypes with respect to their ability to detoxify these agents. The present study was conducted to determine whether GSTM1 and GSTTl gene polymorphism influences the development of diabetic nephropathy in type 2 DM. The study population consisted of 80 subjects divided into 30 patients type 2 DM with diabetic related end-stage renal diseases [ESRD], 30 patients type 2 DM without nephropathy and 20 subjects apparently healthy individuals as a controls. Multiplex polymerase chain reaction [PCR] was used to analyze GSTM1 and GSTTl polymorphism. GSTTl and GSTM1 gene polymorphism occur more in diabetic patients with ESRD than diabetic patients without nephropathy [GSTM1 null genotype was present in 63% while GSTTl null genotype was present in 60% in group I]. Frequency of homozygous deletion of both GSTTl, GSTM1 was higher in diabetic patients with ESRD [53%] than patients without ESRD [10%], or control [5%], [p<0.05]. Significant negative correlation was found between presence of/GSTMl, GSTTl and albuminuria, serum creatinin and blood urea in diabetic patients with ESRD with a positive correlation between presence of gene GSTTl and GSTM1 null genotype and creatinine clearance where creatinine clearance was lower in patients with GSTT1and GSTM2 deletion, GSTM1 and GSTTl null genotype may play a significant role in the aetiopathogeneses and development of diabetic ESRD and may be a useful marker in the prediction of diabetic ESRD. Also, it can drive approch of genetic therapy in prevention of diabetic nephropathy